Hypertension and associated diseases including stroke, atherosclerosis and chronic kidney disease remain the number one cause of death throughout the world. In the United States, more than fifty percent of hypertensive patients do not have their blood pressure under good control; most patients need more than one medication to achieve their target blood pressure. Suboptimal blood pressure control is in part due to poor patience compliance because of the adverse side effects (e.g., dizziness, headache, cough, sexual dysfunction) associated with the widely prescribed angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs).
Angiotensin II (Ang II) inhibitors are in the top ten global therapeutic classes of pharmaceuticals. In 2008, global sales of Ang II inhibitors exceeded $22 billion and sales are expected to reach $30 billion by 2015. Accordingly, there would be great commercial demand for novel Ang II inhibitors/receptor antagonists that have a therapeutic profile that is distinct from ACEi and ARBs; such novel Ang II inhibitors/receptor antagonists could exhibit synergistic effects and/or reduce off-target adverse events (e.g., sexual dysfunction) through lowered dosages.